Silicon-Tethered reactions B A-B Duke m. fitch Evans Group Seminar March 15. 1996 Bols, M; Skrydstrup, T. Chem. Rev. 1995, 95, 1253-1277 Cycloadditions A. 5-Atom Tether Ring 2.区2 3.[5+2] B. 6-Atom Tether Ring C 7-Atom Tether Ring 1. Type I and ll Diels-Alder D. 8-Atom and Larger Tether Rings 1. Type Il Diels-Alder Radical reactions A. 5-EXo-and 6-Endo- Ring Formations 1. Trig-Cyclizations 2. Dig-Cyclizations B. 6-EXo-and 7-Endo-Ring Formations lIL Silicon Addition to double bonds A. Addition to c=c Bonds 1. Hydrosilylation Bis-silylation B. Addition to c=o bonds Ⅳ. Nucleophile Delivery 33A-013/149611:15PM
A + B A + B A B Si A Silicon-Tethered Reactions B Si Duke M. Fitch Evans' Group Seminar March 15, 1996 Review: Bols, M.; Skrydstrup, T. Chem. Rev. 1995, 95, 1253-1277. I. Cycloadditions A. 5-Atom Tether Ring 1. [4 + 2] 2. [2 + 2] 3. [5 + 2] B. 6-Atom Tether Ring C. 7-Atom Tether Ring 1. Type I and II Diels-Alder D. 8-Atom and Larger Tether Rings 1. Type II Diels-Alder II. Radical Reactions A. 5-Exo- and 6-Endo- Ring Formations 1. Trig-Cyclizations 2. Dig-Cyclizations B. 6-Exo- and 7-Endo- Ring Formations C. Others III. Silicon Addition to Double Bonds A. Addition to C=C Bonds 1. Hydrosilylation 2. Bis-silylation B. Addition to C=O Bonds IV. Nucleophile Delivery 33A-01 3/14/96 11:15 PM
Why use a silicon tether? Intramolecularity offers reduced entropic factors Higher yields Certain reactions that could not be carried out intermolecularly are possible u High Regioselectivity Function of tether length Certain cases offer route to opposite regioisomer obtained from intermolecular variant u Increased Stereoselectivity Function of tether length and steric bulk of alkyl substituents on silicon u Functional Group Protection Serves as protecting group before and after reaction Protodesilylation, Tamao oxidation, allylsilane additions, and transmetallations are possible Diels-Alder To Form 5-Atom Tether Ring 60-170°c favors exo-cyclization ieburth S M. Fensterbank, L.J. Org. Chem. 1992, 57, 5279 33A-023/149611:14PM
OH SiR2Cl O Si R R Si O R R Si O R R OH SiR2Cl O Si R R ❏ Increased Reactivity ❏ High Regioselectivity ❏ Increased Stereoselectivity ❏ Functional Group Protection ❏ Facile Refunctionalization H O Si Why use a silicon tether? - Intramolecularity offers reduced entropic factors - Higher yields - Certain reactions that could not be carried out intermolecularly are possible - Function of tether length - Certain cases offer route to opposite regioisomer obtained from intermolecular variant - Function of tether length and steric bulk of alkyl substituents on silicon - Serves as protecting group before and after reaction - Protodesilylation, Tamao oxidation, allylsilane additions, and transmetallations are possible Et3N H O Si 160 - 170 °C + R = Me 2 : 1 R = Ph R = t-Bu 1 : 4 Note: Bulkier substituent favors exo-cyclization Et3N 190 °C + R = Me 4 : 1 R = Ph R = t-Bu >20 : 1 R R R 10 : 1 Sieburth, S. M.; Fensterbank, L. J. Org. Chem. 1992, 57, 5279. 1 : 1 R Diels-Alder To Form 5-Atom Tether Ring: 33A-02 3/14/96 11:14 PM
Trans ition States Further Transformations TBAF or Occus with re entin f cefic steps Tamao oxidation: Organometallics 1983, 2, 1694 Meli R=Me, 75% over 2 steps Occurs with retention of co Stereoselectivity and Regioselectivity 80% 60: 40 mixture of isomers 1 isomer SiMex 160°c75% 2. TBAF-DMF 85% 2. TBAF-DMF 8 Stork, G: Chan, T.Y., Breault, G. A.J. Am. Chem. Soc. 1992, 114. 7578 33A-033/14965:30PM
O H H Si R R H H O Si R R Si O R R OH OH OH OH SiMe3 O SiMe2 exo SiMe2 O endo Transition States: Me Me OH vs. Further Transformations: TBAF TBAF or KF then H2O2 MeLi R = Me or Ph, 71-85% over 2 steps Occurs with retention of configuration O Ph SiMe2 R = Me, 75% over 2 steps Ph OH Tamao oxidation: Organometallics 1983, 2, 1694. R = Me, 75% over 2 steps Occurs with retention of configuration 60:40 mixture of isomers 160 °C 80% TBAF-DMF, 75 °C 65% O SiMe2 Stereoselectivity and Regioselectivity: OH 1. 160 °C 75% 2. TBAF-DMF 85% 1. 180 °C 80% Ph 2. TBAF-DMF 85% Stork, G.; Chan, T. Y.; Breault, G. A. J. Am. Chem. Soc. 1992, 114, 7578. Ph 1 isomer 33A-03 3/14/96 5:30 PM
Stork Delivers more siMe, TBAF-DMF °c75% then H2O2 80% TBAF-DMF TBAF-DMF CO Et CO,Et hen H2O2 CoEt Note ed compound is epimerized by fluoride ion in the course of desilylation other Interesting Examples from Sieburth KE.Ho 1: 1 mixture of diastereomers 46%2s06 33A-043/149611:31PM
O SiMe2 CO2Et SiMe2 O CO2Et SiMe2 O CO2Et O SiMe2 CO2Et OH CO2Et OH OH CO2Et OH CO2Et OH CO2Et OH 80 °C 90% O O O SiPh2 O O H Si Ph Ph O SiPh2 O H H O OH OH H Stork Delivers More: TBAF-DMF then H2O2 80% TBAF-DMF then H2O2 TBAF-DMF 60 °C 75% O SiMe2 Note: Selectivity in each case results from endo-addition with respect to the ester, even when the product contains four contigous cis stereocenters. This highly strained compound is epimerized by fluoride ion in the course of desilylation. 190 °C retro-Diels-Alder Bu TBAF-DMF 60 °C ‡ SiMe2 O hetero-Diels-Alder 1 isomer Bu KF, H2O2 75%, 2 steps Other Interesting Examples from Sieburth: SiMe2 O 190 °C 1:1 mixture of diastereomers Bu DDQ 46%, 2 steps 33A-04 3/14/96 11:31 PM
Silicon Connected to Diene 1 mol% Ni(acac)2 2 mol% DIBAK-H H-SiMez(NEt2) 52% z·E=94:6 1n1 KF, H2O2 ' ph Tamao, K; Kobayashi, K; Ito, Y J. Am. Chem. Soc. 1989, 111, 6478 Photochemical [2+2 Note: Similar results were obtained with a four s necessary to prevent Baeyer-Villiger oxidation R= Me n-CsH REP Formal [5+2: 1 isomer 89, 3 steps Note: Intermolecular vanant failed to react Rumbo, A; Castedo, L; Mourino, A; Mascarenas, J. L.J. Org. Chem. 1993, 58, 5585 33A-053/14965:33PM
H H SiMe2(NMe2) HO Ph Si O Ph Ph Me2Si O Ph OH OH O CO2Me R O Si Ph Ph O O Si CO2Me H R Ph Ph O O Si CO2Me H R Ph Ph + H-SiMe2(NEt2) O O BzO OH 1 mol% Ni(acac)2 2 mol% DIBAl-H benzene, 50 °C 52% Z:E = 94:6 + Et2O, r.t. 10 h O O BzO O 1 isomer KF, H2O2 75%, 3 steps Silicon Connected to Diene: xylene SiMe2 Tamao, K; Kobayashi, K; Ito, Y. J. Am. Chem.Soc. 1989, 111, 6478. ClMe2Si Photochemical [2+2]: Crimmins, M. T.; Guise, L. E. Tet. Lett. 1994, 35, 1657. O O SiMe2 O + hν, >350 nm 70-80% BzO R = n-C5H11 R = Me R = Ph H 90 : 10 85 : 15 >95 : 5 O OH 170 °C O Note: Similar results were obtained with a four atom tether. Also, for the subsequent Tamao oxidation, protection of the ketone was necessary to prevent Baeyer-Villiger oxidation. BzO 1 isomer Formal [5+2]: KF m-CPBA OH Et3N 78%, 3 steps Rumbo, A.; Castedo, L.; Mourino, A.; Mascarenas, J. L. J. Org. Chem. 1993, 58, 5585. Note: Intermolecular variant failed to react. 33A-05 3/14/96 5:33 PM